Dynamics and phylogenetic relationships of HIV-1 transmitted drug resistance according to subtype in Italy over the years 2000-14

Background: Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care.Methods: In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters.Results: Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005-14: 19.5%-38.5%, P<0.0001), particularly among Italians (<2005-14: 6.5%-28.8%, P<0.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005-14: 2%-7.1%, P=0.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005-14: 12.9%-33.5%, P=0.001) and non-B subtypes (<2005-14: 18.4%-41.9%, P=0.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005-14: 14.3%-35.5%, P=0.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6-19) versus 4 (3-4), P=0.047].Conclusions: The epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multitransmitters is a major target for controlling HIV spread.